Jun Zhang, Qian Yun, Yuhan Dai, Mengmeng Zheng, Zhi Lin, Zixin Deng, Xudong Qu, Chun Lei
{"title":"Trifluoromethylation of Antimycin via Extender Unit Incorporation Improves Antifungal Potency","authors":"Jun Zhang, Qian Yun, Yuhan Dai, Mengmeng Zheng, Zhi Lin, Zixin Deng, Xudong Qu, Chun Lei","doi":"10.1021/acs.orglett.5c01134","DOIUrl":null,"url":null,"abstract":"We report the first biosynthesis of trifluoromethyl (TFM)-containing extender unit and its incorporation into the polyketide biosynthetic pathway. Using engineered enzymes UkaQ<sup>FAV</sup> and Arm13-ACCase, we synthesized a TFM-containing extender unit, which was successfully integrated into the antimycin structure. This modification resulted in stereochemical changes, leading to the formation of an unusual 7<i>S</i>-epimer. The TFM-modified antimycin derivatives exhibited significantly enhanced antifungal activity, providing a new strategy for polyketide diversification and drug development.","PeriodicalId":54,"journal":{"name":"Organic Letters","volume":"17 1","pages":""},"PeriodicalIF":5.0000,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Organic Letters","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.1021/acs.orglett.5c01134","RegionNum":1,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, ORGANIC","Score":null,"Total":0}
引用次数: 0
Abstract
We report the first biosynthesis of trifluoromethyl (TFM)-containing extender unit and its incorporation into the polyketide biosynthetic pathway. Using engineered enzymes UkaQFAV and Arm13-ACCase, we synthesized a TFM-containing extender unit, which was successfully integrated into the antimycin structure. This modification resulted in stereochemical changes, leading to the formation of an unusual 7S-epimer. The TFM-modified antimycin derivatives exhibited significantly enhanced antifungal activity, providing a new strategy for polyketide diversification and drug development.
期刊介绍：
Organic Letters invites original reports of fundamental research in all branches of the theory and practice of organic, physical organic, organometallic,medicinal, and bioorganic chemistry. Organic Letters provides rapid disclosure of the key elements of significant studies that are of interest to a large portion of the organic community. In selecting manuscripts for publication, the Editors place emphasis on the originality, quality and wide interest of the work. Authors should provide enough background information to place the new disclosure in context and to justify the rapid publication format. Back-to-back Letters will be considered. Full details should be reserved for an Article, which should appear in due course.
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